1 State University of New York Downstate Medical Center, Children's Hospital at Downstate, Department of Pediatrics, Division of Pediatric Endocrinology, Brooklyn, NY 11203 USA

2 Institute of Molecular Medicine and Genetics, The Medical College of Georgia, Section of Reproductive Endocrinology, Infertility, and Genetics, Department of Obstetrics and Gynecology, Augusta, GA 30912, USA

3 State University of New York Downstate Medical Center, Department of Pathology, Division of Molecular Pathology, Brooklyn, NY 11203, USA

Abstract

CHARGE is a phenotypically heterogeneous autosomal dominant disorder recognized as
a cohesive syndrome since the identification of CHD7 as a genetic etiology. Classic features include: Coloboma, Heart defects, Atresia
choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies
and/or deafness. With greater accessibility to genetic analysis, a wider spectrum
of features are emerging, and overlap with disorders such as DiGeorge syndrome, Kallmann
syndrome, and Hypoparathyroidism Sensorineural Deafness and Renal Disease syndrome,
is increasingly evident. We present a patient with a unique manifestation of CHARGE
syndrome, including primary hypoparathyroidism and a limb anomaly; to our knowledge,
he is also the first CHARGE subject reported with bilateral multicystic dysplastic
kidneys. Furthermore, with structural modeling and murine expression studies, we characterize
a putative CHD7 G744S missense mutation. Our report continues to expand the CHARGE phenotype and highlights
that stringent fulfillment of conventional criteria should not strictly guide genetic
analysis.